Extraembryonic expression of EPCR is essential for embryonic viability
Extraembryonic expression of EPCR is essential for embryonic viability
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DOI：
10.1182/blood-2005-01-0406
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发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Esmon, CT
中科院分区：
文献类型：
--
作者：
Li, WH;Zheng, XZ;Esmon, CT
内皮细胞蛋白C受体（EPCR）通过凝血酶-血栓调节蛋白复合物增强蛋白C的激活。小鼠EPCR基因（Procr）的缺失导致胚胎10天（E10.0）前胚胎死亡。从E7.5开始，在胎母边界的巨滋养细胞中检测到EPCR，而从E13.5开始，在胚胎主动脉内皮细胞中检测到EPCR，这表明胚胎外EPCR的表达可能对胚胎存活至关重要。使用条件敲除策略，我们证明胎盘巨滋养细胞上表达EPCR的procr缺陷胚胎可以被携带至足月，然后正常发育。相反，EPCR在胚胎中表达，而在巨滋养层细胞中不表达，并不能拯救小鼠。在组织因子活性低的转基因小鼠中，Procr缺乏对胚胎并不致命。成年后，procr缺陷小鼠在促凝剂刺激下产生更多凝血酶，激活更少的蛋白C。自发凝血酶形成缺陷的动物随着年龄的增长而增加。这些发现表明胚胎外EPCR表达对胚胎发育至关重要。
The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thrombomodulin complex. Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality before embryonic day 10 (E10.0). EPCR is detected in the giant trophoblast cells at the feto-maternal boundary from E7.5 and weakly in embryonic aortic endothelial cells from E13.5, suggesting that extraembryonic EPCR expression may be essential for embryonic viability. Using conditional knock-out strategies, we demonstrate that Procr-deficient embryos with EPCR expression on placenta giant trophoblasts can be carried to term and then develop normally. Conversely, EPCR expression in the embryo, without expression in the giant trophoblast cells, does not rescue the mice. In genetically modified mice with low tissue factor activity, Procr deficiency is not lethal to the embryo. As adults, Procr-deficient mice generate more thrombin and activate less protein C in response to procoagulant stimuli. Spontaneous thrombin formation in the deficient animals increases with age. These findings show that extraembryonic EPCR expression is critical for embryo development.